Long non‑coding RNA NEAT1 modifies cell proliferation, colony formation, apoptosis, migration and invasion via the miR‑4500/BZW1 axis in ovarian cancer

Mol Med Rep. 2020 Oct;22(4):3347-3357. doi: 10.3892/mmr.2020.11408. Epub 2020 Aug 4.

Abstract

Ovarian cancer (OC) is a frequently occurring malignant tumor in women. Increasing evidence has indicated that long non‑coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) participates in OC pathogenesis. Thus, the aim of the present study was to explore the function of NEAT1 during OC progression. The expression levels of NEAT1, microRNA (miR)‑4500 and basic leucine zipper and W2 domain‑containing protein 1 (BZW1) were assessed via reverse transcription‑quantitative PCR and western blotting. Furthermore, cell proliferation, colony formation, apoptosis, migration and invasion were assessed using Cell‑Counting Kit 8, colony formation, flow cytometry and Transwell assays, respectively. Cell glycolysis was analyzed using an XF96 metabolic flux analyzer, and the relationship between miR‑4500 and NEAT1 or BZW1 was verified via dual‑luciferase reporter and RNA binding protein immunoprecipitation assays. miR‑4500 expression levels were low, whereas NEAT1 expression levels were high in OC tissues and cell lines compared with control tissues and cell lines. Moreover, the results indicated that NEAT1 was a sponge of miR‑4500, which directly targeted BZW1. NEAT1 knockdown induced OC cell apoptosis, and inhibited OC cell proliferation, colony formation, migration, invasion and glycolysis. miR‑4500 inhibitor reversed NEAT1 knockdown‑mediated effects. Similarly, miR‑4500 mimic‑mediated effects on cell functions were reversed by BZW1 overexpression. In addition, the results indicated that BZW1 expression was regulated by NEAT1 and miR‑4500. Collectively, the present study suggested that NEAT1 modulated cell proliferation, colony formation, apoptosis, migration, invasion and glycolysis via the miR‑4500/BZW1 axis in OC; therefore, NEAT1 may serve as a therapeutic target for OC.

MeSH terms

  • Apoptosis
  • Case-Control Studies
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycolysis
  • Humans
  • MicroRNAs / genetics*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • RNA, Long Noncoding / genetics*

Substances

  • BZW1 protein, human
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • MicroRNAs
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • microRNA 4500, human